Self-injurious behavior (SIB) is a potentially life-threatening and extremely costly form of psychopathology affecting persons with mental retardation. Most investigators agree that SIB in persons with mental retardation can be maintained by operant and/or biologic factors; however, integrative diagnostic and treatment models have yet to be developed. The investigators' aims for this project are threefold. First, they propose to determine the extent to which their bio-behavioral model can reliably classify three subtypes of self-injurious behavior as (1) operant, (2) possibly biologic, or (3) mixed operant and possibly biologic. Second, they propose to assess the extent to which bio- behavioral classification of SIB predicts the differential effectiveness of behavioral and pharmacologic treatments. Third, the investigators plan to identify clusters of observable clinical features and neurochemical markers that distinguish different subtypes of possibly biologic and mixed SIB which may enhance prediction of effective pharmacologic treatment. There are four major phases to this study: (1) Diagnostic Phase, (2) Treatment Phase, (3) Parent and Family Training, and (4) Aftercare and Follow-Up. In the Diagnostic Phase, SIB cases will be differentially diagnosed as operant, possibly biologic or mixed operant and possibly biologic and then subtyped within each classification. The Treatment Phase will expose subjects to either behavioral, pharmacologic, or combined behavioral and pharmacologic treatments and assess whether treatment efficacy differs by SIB classification. During the Parent and Family Training Phase, parents/care providers and other family members will be systematically trained to implement the most effective combination of behavioral and pharmacologic treatments for their child's SIB. The study will conclude with 24-month Aftercare and Follow-Up Phase consisting of periodic community-and hospital-based assessments, parent training, and medical care. The effects of behavioral and pharmacologic treatments, parent and family training, and aftercare therapy will be evaluated on the following dependent variables: (a) rate of self-injurious behavior, (b) appropriate activity engagement, (c) functional communication, (d) adaptive behavior scales, (e) tissue damage caused by SIB, (f) medication side-effects, and (g) social validity measures. Bio- behavioral diagnostic procedures will classify SIB cases as operant, possibly biologic, or mixed. All subjects within these diagnostic groups will start on placebo and then be randomly assigned to one of the following treatment conditions (a) behavioral treatment plus placebo, (b) medication, or (c) behavioral treatment plus medication. Patients, parents, and most investigators will be blinded to the treatment condition in effect. A 3 x 3 factorial experimental design will be used to compare the effectiveness of the different treatments. Data analysis will be by analysis of variables (ANOVA) and planned comparison tests. Empirical cluster analysis will identify distinct subtypes of possibly biologic SIB.